Sean Wu.

Abstract

HomeCirculation ResearchVol. 124, No. 10Sean Wu Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBSean WuDevelopment at the Heart of Science Jaclyn M. Jansen Jaclyn M. JansenJaclyn M. Jansen Search for more papers by this author Originally published9 May 2019https://doi.org/10.1161/CIRCRESAHA.119.315208Circulation Research. 2019;124:1417–1419At its origin, the heart is like all organs, a mass of undifferentiated cells in a growing embryo. Through a series of highly coordinated signals, a small number of cells within that population begin to change, adopting unique cell fates that ultimately form a fully functioning heart. Sean Ming-yuan Wu, MD, PhD, has dedicated his research to identifying and understanding the signals that trigger this morphogenesis. Drawing from experience in diverse fields, such as engineering, and molecular and stem cell biology, Wu is laying the foundation for work that may someday lead to breakthroughs in tissue engineering.Wu, now Associate Professor of Medicine and, by courtesy, Pediatrics at Stanford University, began his research career as a graduate student studying vascular biology in the laboratory of Salvatore Pizzo at Duke University School of Medicine. He focused on the very earliest stages of atherosclerosis, when macrophages trigger inflammation and, in turn, oxidation in the blood vessel. Wu found that oxidation prevents the removal of key clotting inhibitors from the bloodstream during and after atherosclerosis, increasing clots and worsening outcomes.1After completing his graduate and medical degrees, Wu moved to Harvard Medical School to work with Stuart Orkin, a world-renowned hematologist. Although stem cell biology was a nascent field, hematologists had long appreciated that hematopoietic stem cells are able to give rise to the full complement of cell types within blood. Wu borrowed from the field of hematology for a decidedly developmental approach to cardiology. His work identified the earliest embryonic progenitor cells that are able to give rise to key cell populations that will ultimately develop into heart muscle and blood vessel cells.2In his independent lab at Massachusetts General Hospital (MGH), Wu explored the signals and molecules that regulate the formation of the heart. He focused initially on identifying the earliest upstream regulators that are necessary to make embryonic progenitor cells. Wu found that the transcription factor YY1 (Yin Yang 1) is a critical regulator of this process. Without the gene, the embryo fails to form a heart and dies very early.3The work was surprising: previous research had demonstrated that YY1 serves as a repressor of the genes that define muscle cells.4 In contrast, Wu found that YY1 activates the expression of precursor genes for heart muscle during much earlier developmental timepoints. In fact, further research revealed that YY1 acts as a maintenance factor for primitive progenitors of the heart. Sustained expression of the gene causes cells to remain in an immature state.5 The work established multifaceted roles for YY1 which are dependent not just on cell type but also on developmental time.In 2012, Wu moved to Stanford University where he continues to explore cellular differentiation during heart development. His lab has recently described the genome-wide transcriptome of the developing and postnatal heart at single cell resolution6,7 and the creation of cardiac patient-disease models using induced pluripotent stem cells. At the same time, in work supported by a National Institutes of Health Director’s Pioneer Award, he is collaborating with bioengineers and material engineers to create vascularized tissues using three-dimensional bio-printers. This work will likely be broadly applicable: the primary limitation in many engineered tissues, from heart to lung to kidney, is a lack of blood vessels required for such tissues to stay alive.In a recent conversation with Circulation Research, Wu described his development and career as a scientist. Both in his life and his research, he has taken a uniquely broad and adaptable approach that has helped him become a leader in developmental cardiology.Where Did You Grow Up?I was born in Taiwan and, after spending grade school there, I moved to the United States. My dad was finishing his graduate work at the University of Arkansas, so that’s where I lived when we first arrived. I was like many other immigrant children—I learned the language and met people on the playground, playing sports.After my dad finished with his graduate training, we moved to San Diego. My dad became a postdoc and then junior faculty at San Diego State University. I then moved to Stanford for college.What Was Your Family Like When You Were Growing Up?My dad is in physics. He worked on laser optics as his research field. His faculty position in San Diego was brief and he soon took a professorship in Taiwan. In Asia, a professorship is more heavily focused on teaching than research because research resources are usually not as extensive as in the United States.My mom is a grade school teacher. Growing up in that environment, it felt natural to be an academic. My sister also ended up in teaching—opening a tutoring company for middle and high schoolers.Did You Become Interested in Science at a Young Age?Like most kids, I was really curious about everything, especially anything related to technology or mechanics. I was sort of a little toy builder.I was always asking: how does it work? Even in first or second grade, when I saw something intricate and interesting, I wanted to know what made it work. That extensive curiosity has always driven me, and it seems fairly natural that I gravitated towards science.When Did You Decide You Wanted to be a Cardiologist?I did my medical training at Duke University. Originally, I thought I was going to be an orthopedic surgeon which fit well with my undergraduate degree in mechanical engineering and my thesis research in biomechanics. But during my clinical rotation as a medical student, I was struck by the tremendous number of people with heart disease in the hospital Intensive Care Unit. There were very few treatments available. It was profound for me to see that we really needed to understand what was going on with heart disease and particularly with myocardial infarction from atherosclerosis. That clinical training experience helped me decide to go into a lab that studies vascular biology.After my MD/PhD training, I stayed at Duke and did two years of the internship and residency in internal medicine. I then moved to Boston for my cardiology fellowship at MGH. I had two years of clinical training in cardiology at MGH, then I moved to Boston Children’s Hospital for my research training, where I worked on heart development in Stuart Orkin’s lab. When I finished my postdoctoral research fellowship at Boston Children’s Hospital, I went back to MGH to start my own research lab.Download figureDownload PowerPointSean WuWhy Did You Move From MGH to Stanford?The first reason was family. My wife and I met at Stanford as undergrads, and we both still have family members here in the Bay area. Neither of us has family in Boston, but coming to Stanford allowed us to be closer to our siblings and cousins.The second reason we moved was to expand our research and clinical work. My wife is also an academic. She’s an endocrinologist. She did her MD/PhD at Duke with me and was also at MGH. Now we are both physician-scientists here at Stanford. Since my wife and I were both at Stanford as undergrads, we were familiar with the supportive research environment here.What Makes a Supportive Research Environment?In part, it has to do with proximity. Here at Stanford, all of the research activity is fairly centralized so that if you need to find a bioengineer, the Bioengineering Department is just a two-minute walk, three buildings over. If you wanted to find someone in physics or computer science, they’re about five minutes away, just a little bit over in the engineering quad. Boston was great with many tremendously talented scientists throughout the city. Still, it was not as easy to collaborate as it is now, with people who are literally next door or just down the hall.How Did You and Your Wife Deal With the Two-Career Problem During Your Move?My wife and I are committed to a two-career family. We make decisions equally about who is taking care of what in the family for the career and the moves.The two career move definitely is challenging because I think both of us tried to be sensitive to the needs of each other. We wanted to find an institution where we both felt like we were being recruited and not just one person following the other.How Do You Balance Your Home Life as Two Physician-Scientists?We have two girls, one is 19 and has started college, and the other is 14 and in eighth grade. From the beginning, we have had a lot of help from family. Very early on, my parents made an offer to come and take care of our kids, so of course, we accepted.This may be a part of the Chinese culture—with parents feeling some sense of responsibility—although it’s definitely not universal in every Asian family. But, that’s the way my parents and also my wife’s parents felt. My wife’s family also originally came from Taiwan.Their offer allowed us to have our first child when my wife was still in medical school, and I was just starting my internship in internal medicine at the time.Trainees often ask me and my wife if there is a best time to have kids. The answer is that there really is not ever one best time. Trainees sometimes think they should wait until after residency or fellowship or until they become faculty or they are tenured. But things seem to just keep getting busier. If you wait for tenure, sometime it works out, but other people may not necessarily feel like they want to wait that long.When you make the decision that you’re going to have a child someday, that is the time to go ahead and have a child. It doesn’t ever get easier. You then have to decide how you want to balance your career and what sort of time and sacrifice you are willing to make in your career to spend time with your child.What Are Your Hobbies Outside of the Lab?My wife and I try to maintain our regular exercise. It’s become more difficult to play sports with others, like tennis and basketball. So now, I run. Whenever I have the time I just get up, go out, and run.I also have exercise equipment at home. With kids, we realized that during the day you are working and then you have to take care of homework and everything else. By the time they go to bed, it is 10:00 or 11:00 at night and we finally get to exercise.We also love traveling. We’ve done a lot of traveling with the kids, and even with our extended family. We have this gigantic caravan of 14 or 15 people. These family travels around the world have been quite interesting. We also travel with friends and colleagues. Just this summer, we did a safari trip in Kenya with my colleague Joseph Wu. It was around the time of the annual migration of all the wildebeests. We were able to see lions and elephants and giraffes. It was really nice.How Hard Would You Say You Work?Before I give a number, I would say that one thing the trainees don’t always realize is the flexibility of your work hours when you are a scientist. This might be more relevant for people that are choosing between academia and medical practice, but I think people focus too much on salary difference between clinical medicine and research, and not enough on the benefit of work hour flexibility.As an example, if you need to go do things like take the kids to the dentist or go see a kid’s soccer game, you have the flexibility in research to do that. With clinical practice, you need to be present to care for your patients at all times.In my day-to-day, I try to do as much work as I can, and everything else then fits in around it. I start the day around 8:00 am. When I’m in the office, I’m either doing my clinical practice or I’m doing my research work. I spend about 15% of my time with patients but the rest is research. As with most academics, that means reviewing and writing papers and grants, responding to emails and teaching, doing administrative work and organizing. I meet with each of my lab members on a weekly or bi-weekly basis so that I can make sure everyone in the lab is progressing. I want them to have the opportunity to ask me questions and troubleshoot.I continue that until 7:00 pm or so, when I head home. Usually, I continue some work at home but it is in between what’s going on with our kids and their homework and getting them to bed. Then, depending on how busy things are, I exercise, or if it’s really necessary, I’ll continue my work until I go to bed.Is it Difficult to Work Such Long Hours?Yes, at first, but once I got used to it, it became fairly standard. When I was in college, I spent a lot of time studying for tests, but when I didn’t have tests then I had lot of free time. In med school, it felt like the screw was tightened up a little bit. We had to work more with classes or being in the hospital. Still, I had some break and vacation time.When I began my residency clinical, the screw was tightened even further. I was literally working 36 hours straight because it was before they instituted work restrictions. You start at 7:00 in the morning, you work all day, pick up everybody else’s patients at 7:00 at night, work all night, and then start a full work day the next morning, just like everybody else. I’m glad that people no longer do this. There was definitely tremendous burnout among physicians because of the hours that were expected.In comparison to residency, I feel like everything else is pretty easy. Over the years, my work pattern has become my steady state, and I don’t necessarily think of it. When you really like what you’re doing, it doesn’t feel like you’re working.Many of us in academia are here because we are very interested in the science, the medicine, or the translation between the two. A lot of times it doesn’t feel like you’re doing work because it’s what you naturally gravitate toward anyway.Is There Anything You Wish You Had Done Differently in Your Career?I wish I had connected more with colleagues in other fields. I always find I learn a lot from people who are doing science in different fields. I feel like I spend a whole lot of my time in the details of what goes on in the cardiovascular field, which is to some extent a necessity, but it prevents me from being able to learn about how people do things in other fields. And it is incredibly beneficial to work across disciplines, like I did when I was working in a hematology lab.What Advice Do You Have for Young Scientists?During PhD training, the most important things is to find a good mentor. Your mentor must be willing to train you, support you, and encourage you. And she or he must give you the freedom to explore interesting science that hasn’t been well understood.At every stage of your career, you certainly have to put in a fair amount of effort. But you also have to be very inquisitive, curious, and want to learn more. You need to be fascinated by what is new and you need to want to learn.You also can’t be afraid to try new things. Curiosity motivates you, but you can’t be afraid of failing. In science, we fail all the time. You write grants, you don’t get them, and you re-submit again. The same is true with papers. Failure is just part of what you do in science. But you can’t get too hung up about that aspect.You have to keep looking forward, keep being interested and curious about new things, keep trying and not worry about the failure. Together, this will make you successful in science.DisclosuresNone.